Inhibitory effects of trimetazidine dihydrochloride on aggregation, serotonin release and malondialdehyde production in rabbit platelets.

Aggregation, serotonin release and malondialdehyde (MDA) production via cyclooxygenase and thromboxane A2 synthetase were investigated in rabbit platelets. Trimetazidine dihydrochloride (TMZ) attenuated the collagen-induced aggregation more strongly than the arachidonic acid (AA)-, thromboxane A2 agonist (U-46619)-, Ca2+-ionophore (A-23187)- and ADP-induced aggregation: IC50 values were 1.0 +/- 0.1, 4.4 +/- 0.3, 4.3 +/- 0.4, 4.1 +/- 0.7 and 3.3 +/- 0.2 mM, respectively. TMZ decreased dose-dependently the serotonin release induced by collagen and A-23187, but did not decrease that induced by AA. TMZ also decreased the MDA production induced by collagen and A-23187 (IC50: 0.3 +/- 0.03 and 1.0 +/- 0.1 mM, respectively), but did not decrease the production induced by AA. Furthermore, TMZ decreased dose-dependently the MDA production induced by exogenous phospholipase A2. On the other hand, indomethacin (10 microM) attenuated the aggregation induced by collagen and AA, but not by the other agents, and decreased the serotonin release and the MDA production induced by collagen, A-23187 and AA. The present results suggest that TMZ may inhibit the process preceding the cyclooxygenase pathway in the AA cascade, and subsequently may attenuate the aggregation and the serotonin release via thromboxane A2 production from endogenous AA.